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Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin

tetano

Editor, Senior Moderator
Immunity. 2019 Jul 16. pii: S1074-7613(19)30294-8. doi: 10.1016/j.immuni.2019.06.024. [Epub ahead of print]
[h=1]Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin.[/h] Andrews SF[SUP]1[/SUP], Chambers MJ[SUP]2[/SUP], Schramm CA[SUP]2[/SUP], Plyler J[SUP]2[/SUP], Raab JE[SUP]2[/SUP], Kanekiyo M[SUP]2[/SUP], Gillespie RA[SUP]2[/SUP], Ransier A[SUP]2[/SUP], Darko S[SUP]2[/SUP], Hu J[SUP]2[/SUP], Chen X[SUP]2[/SUP], Yassine HM[SUP]3[/SUP], Boyington JC[SUP]2[/SUP], Crank MC[SUP]2[/SUP], Chen GL[SUP]2[/SUP], Coates E[SUP]2[/SUP], Mascola JR[SUP]2[/SUP], Douek DC[SUP]2[/SUP], Graham BS[SUP]2[/SUP], Ledgerwood JE[SUP]2[/SUP], McDermott AB[SUP]4[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Vaccine-induced memory B cell responses to evolving viruses like influenza A involve activation of pre-existing immunity and generation of new responses. To define the contribution of these two types of responses, we analyzed the response to H7N9 vaccination in H7N9-naive adults. We performed comprehensive comparisons at the single-cell level of the kinetics, Ig repertoire, and activation phenotype of established pre-existing memory B cells recognizing conserved epitopes and the newly generated memory B cells directed toward H7 strain-specific epitopes. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus.
Published by Elsevier Inc.


[h=4]KEYWORDS:[/h] H7N9; Ig repertoire; Tbet; activated B cells; hemagglutinin; influenza; memory B cells; vaccine response

PMID: 31350180 DOI: 10.1016/j.immuni.2019.06.024
 
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